Fluorophotometry

Klein, Ronald; Engerman, Ronald L.; Ernest, J. Terry

doi:10.1001/archopht.1980.01020041085020

Cited by 18 publications

(3 citation statements)

References 7 publications

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“…Although guinea pigs have been previously used as a diabetes model only through induction with STZ, this serves specifically as a model of insulin-dependent diabetes because it lacks the contribution of insulin resistance. Moreover, there are substantial differences published in the overall susceptibility of the guinea pig to chemical induction of diabetes with STZ, which are the consequence of a wide range of experimental approaches ( Wehner and Majorek, 1975 ; Klein et al, 1980 ; Schlosser et al, 1984 , 1987 ; Aomine et al, 1990 ; Lenzen, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

Podell

Ackart

Richardson

et al. 2017

Disease Models &Amp; Mechanisms

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Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species.

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Section: Introductionmentioning

confidence: 99%

A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

Podell

Ackart

Richardson

et al. 2017

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Evidence to support the increased vascular permeability concept is the finding of penetration of the junctions by horse-radish peroxidase in alloxan-diabetic dogs (Wallow & Engerman 1977). Caution is necessary, however, in interpreting these findings as irrefutable evidence of a defective blood-retinal barrier because it has not been ruled out that the fluorescent dye enters the vitreous from the aqueous fluid (Klein et al 1980) as opposed to the retina. But, whatever the origin of leakage, the beneficial effect of normoglycaemia on the retinal lesions and intravitreal dye accumulation suggests that metabolic factors are of major pathogenetic importance.…”

Section: Pathophysiology -Preliminary Stagementioning

confidence: 44%

“…But in early diabetes the amount of fluorescein entering the vitreous after injection into the systemic circulation is increased. Whether this represents increased permeability of the retinal vessels as originally suggested by Cunha Vaz et al (1975) or a fault in the pigment epithelium (Tso et al 1980) is unresolved, although in support of the latter hypothesis is the description by Klein et al (1980) of a similar increase in vitreal fluorescein in guinea-pigs with streptozotocininduced diabetes, since that species is essentially devoid of intraretinal blood vessels. Also there are reports of altered membrane permeability (Kirber et al 1980) and morphological changes (Tso et al 1980) in the pigment epithelium.…”

Section: Pathophysiology -Preliminary Stagementioning

confidence: 44%